| First Author | Wu T | Year | 2023 |
| Journal | PLoS Genet | Volume | 19 |
| Issue | 1 | Pages | e1010630 |
| PubMed ID | 36706168 | Mgi Jnum | J:333147 |
| Mgi Id | MGI:7433729 | Doi | 10.1371/journal.pgen.1010630 |
| Citation | Wu T, et al. (2023) Filamin C is Essential for mammalian myocardial integrity. PLoS Genet 19(1):e1010630 |
| abstractText | FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (FlncgKO) and cardiomyocyte-specific knockout (FlnccKO) mice died in utero from severely ruptured ventricular myocardium, indicating filamin C is required to maintain the structural integrity of myocardium in the mammalian heart. Contrary to the common belief that filamin C acts as an integrin inactivator, we observed attenuated activation of beta1 integrin specifically in the myocardium of FlncgKO mice. Although deleting beta1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both beta1 integrin and filamin C from cardiomyocytes resulted in much more severe heart ruptures than deleting filamin C alone. Our results demonstrated that filamin C works in concert with beta1 integrin to maintain the structural integrity of myocardium during mammalian heart development. |
